The invention relates to an apparatus for the examination of a liquid medium, especially for blood analysis in general and more particularly to an improved method and apparatus of this type.
Arrangements which include a measuring sensor which is coupled to a liquid medium to be analyzed as well as to a reference sensor and a pump, and to a liquid calibrating medium and which also include a device for measuring any differences between what is detected by the measuring sensor and what is detected by the reference sensor are known.
An electro-chemical determination of blood parameters can be substantially simultaneous to the drawing of blood from a patient who is to be monitored.
The concentrations of important blood electrolytes, such as calcium Ca.sup.2+, potassium K.sup.+, and sodium Na.sup.+, or the concentration of blood gases, for instance, carbon dioxide or oxygen, or also the pH value or the presence of biomolecules such as glucose, as well as changes in these concentrations and values over time, are measured. Calcium controls various biological processes in the body, for instance, muscle contraction and the release of hormones. The clinical determination and adjustment of such concentrations can therefore be of great importance.
An ion-sensitive field effect transistor is suitable as a measuring sensor. This sensor can be integrated on a silicon chip. A control electrode serves as a membrane which forms a boundary surface to the medium to be analyzed. An electrical potential change related to the concentration to be detected is measured by a shift of ions at the boundary surface formed by the electrode. This measuring probe is known as an ISFET or ChemFET. The probe is directly connected in an alternating fashion to the medium to be analyzed, and a calibration solution. For purposes of discussion the medium to be analyzed is considered to be blood.
A valve releases either a stream of blood or the calibration solution and the released fluid flows through a heat exchanger. The heat exchanger cools the blood to room temperature. An electro-chemical reference electrode can be provided as a reference sensor. It may consist substantially of a metal electrode which is coated with a hard-to-dissolve salt of the metal. The electrode is immersed in an electrolyte solution and is closed off by a diaphragm. The reference sensor is arranged behind the ChemFET, the measuring probe, in relation to the flow direction of the blood. It can pptionally also be connected via a bridge electrolyte and a further diaphragm to the solution under analysis. While such a measuring arrangement makes possible an on-line measurement of a solution in an ex vivo arrangement of the sensor, the blood flow in the feed line hesitates during the calibration. The hesitation of the flow of the blood necessitates heparinization. In addition, the entire setup is relatively complicated. (Med. and Biol. Engineering and Computing, July 1985, pages 329 to 338).
In a further known embodiment of a measuring arrangement for blood analysis, a ChemFET is provided as a measuring sensor which is arranged at the end of a catheter at its inside wall. This measuring sensor is connected via a hose line to an electro-chemical reference electrode as well as through a reversible pump to a container that holds a calibration medium. The reference electrode is connected via a further reversible pump to an infusion solution or a flushing medium. By the pumps, in conjunction with valves, blood or the calibration medium or the flushing medium is alternatingly fed to the measuring sensor. In this embodiment, the calibration medium, as well as the flushing medium must be suitable for injection into the blood circulation of the patient. Interfering potentials can cause a polarization of the reference electrode and can thereby falsify the result of the measurement (German Patent No. 30 38 883).
It is furthermore known that in an arrangement for blood examination, a first ion-sensitive field effect transistor can be provided as the measuring sensor and another transistor can be provided as the reference sensor, between which a solution contact is arranged which is at the null potential of the measuring system. The measuring section of the device is arranged in a catheter. The measuring sensor associated with the measuring section is arranged on the outside of the catheter in the blood stream and remains in the blood track. In this arrangement, the sensor can be covered up by resting against the wall of the blood track and the function of the sensor can thereby be inhibited. Furthermore, the measuring sensor cannot be flushed, and in addition the presence of the sensor may cause a rejection reaction by the body which cannot be prevented. (European Patent OS No. 0 155 725).
A common structural unit can be formed using at least one measuring sensor, a reference sensor, and a measuring channel. Ion-selective electrodes of miniaturized design serve as sensors in the common structural unit design. The measuring channel, connected at one end to the blood stream via a catheter, is connected at the other end to a calibration solution via a reversible pump. For calibrating, the measuring channel is first filled with an infusion solution. Subsequently, blood is drawn into the measuring channel so as to bring the measuring electrode into contact with the blood and then, a different measurement is made. The blood which has been pumped into the measuring channel for the measurement is subsequently returned to the blood stream (U.S. Pat. No. 4,535,786).
In this known arrangement a solution under analysis, or also calibration solutions, which have come into contact with at least one of the sensors, are therefore returned to the patient. This means that the membranes of the sensors must therefore be sterilized. Precautions must be taken against the issuance of toxic substances from the membranes and, also against any separation or degradation of the membrane which can lead to the patient suffering health damage.
It is further known that for the determination of gases, electrolytes or sugar in the blood, a double-lumen catheter can be used. One lumen is connected to an electrode chamber. A separate calibration chamber can be connected to a reversible pump which is directly connected to the other lumen. In the catheter, there is an aperture between the two lumens. The electrode chamber contains a CO.sub.2 or pH electrode, an oxygen electrode and a reference electrode. A carrier solution is pumped in a closed loop and picks up gases from the blood through a gas-permeable wall in the catheter (U.S. Pat. No. 4,221,567).
In a glucose analysis of the blood, a double-lumen needle has already been used for mixing the sample blood with heparin solution. This double channel consists of a thin plastic tube which contains a somewhat shorter inner tube, for removing the heparinized blood stream. The aperture of the inner tube is somewhat set back relative to the opening of the outer tube (Ann. N.Y. Acad. Sc., Vol. 87, (1960), pages 658 to 668).
These known measuring arrangements are complex. In addition, the liquid medium is returned to the sampling point and in some instances so is the infusion solution. This permits substances which have dissolved from membranes of the sensors to get to the sampling. Additional harm can result if the membranes are not sterilized.